e21045 Background: Blood progenitor cells expressing the stem cell marker CD34 have been associated with prognosis in cancer. We hypothesized that non-small cell lung cancer (NSCLC) patients with higher numbers of circulating CD34+ endothelial progenitor cells (CD34+/CD146+/CD45-, CEC) would have worse post-treatment outcomes and patients with more hematopoietic progenitor cells (CD34+/CD45+/CD45dim/CD133+, HPC) would have better outcomes. Methods: Blood samples from patients with advanced NSCLC were analyzed at 3 time points: prior to chemotherapy, after cycle one, and at completion of treatment or progression of disease, in an IRB-approved protocol. CEC, HPC, and immune subsets were measured by flow cytometry optimized for rare event detection. Primary outcomes were progression and death from the time of study entry. Patients were categorized and compared for progression free survival (PFS) and overall survival (OS) based on median cell counts. Differences between groups were tested using log-rank test and Cox regression. Results: A total of 62 patients were enrolled with mean age of 64 (37-87 years). There were 29 deaths after a median follow-up of 8.1 months. 40 patients progressed at a median of 5.4 months. Median numbers of CEC, HPC, and CD4+ T-cells were (0.05/uL, 0.41/uL, and 637/uL, respectively). Lower CEC at baseline was associated with a favorable PFS compared to those with higher counts (median PFS of 7.3 months versus 4.3 months, p=0.049). In a multivariate analysis after adjusting for age, gender, smoking, race, TNM stage, pathology, performance status and CD4 counts at baseline, patients with high CEC had almost 3-fold risk of death (HR=2.70, p=0.04) and disease progression (HR=3.03, p < 0.01) compared with patients with low numbers of CEC. In the same model, patients with fewer CD4+ T cells had > 3 fold risk of death compared with patients with higher numbers (HR=3.79, p=0.01). HPC content was not associated with OS or PFS. Conclusions: In patients with advanced NSCLC, higher CEC and lower CD4 counts at diagnosis are associated with worse outcomes. Higher CEC may serve as a cellular biomarker for extent of disease or tumor biology. Patients with poor T-cell immunity prior to treatment have worse survival.